Obesity Linked to Hyperparathyroidism in Chronic Kidney Disease

Action Points

Explain to interested patients that despite the link between obesity and hyperparathyroidism shown for certain groups of men with chronic kidney disease, it was not clear which was the cause, and which the effect.

The association between BMI and parathyroid levels, found in a study of nearly 500 men, appeared limited to those with features of malnutrition and inflammation, Csaba P. Kovesdy, M.D., of the Salem VA Medical Center here, and colleagues, reported in the September issue of the Clinical Journal of the American Society of Nephrology.

Although obesity has been associated with hyperparathyroidism in patients with normal renal function, the phenomenon was not previously studied in chronic kidney disease, they said.

Because both obesity and hyperthyroidism are complex problems in chronic kidney disease, establishing a relationship between them has potential prognostic and therapeutic implications, they added.

The researchers examined the association between intact parathyroid hormone levels and BMI in 496 male veterans (mean age 69.4, 22.8% black) with chronic kidney disease, stages 2 to 5, who were not yet on dialysis. The estimated glomerular filtration rate (eGFR) was 31.8 Â± 11.2 mL/min per 1.73 m2 .

The men were seen at the VA center from January 1990 to June 30, 2005 and were followed until September 2006.

Higher parathyroid hormone levels were associated with higher BMI after adjustment for age, race, diabetes, and serum calcium and phosphorus levels and proved to be independent of these confounders, the investigators said.

A further analysis found that the association was limited to patients with signs of malnutrition and inflammation. Specifically this included patients with lower albumin (P=0.005 for the interaction term) or higher white blood-cell counts (P=0.026 for the interaction term).

This finding may be unique to patients with chronic kidney disease, the researchers said. Besides providing a possible explanation for why parathyroid hormone levels are higher in obese patients, it may also be important for prognostic reasons, because malnutrition and inflammation are among the major complications responsible for poor outcomes in kidney disease.

The mechanism of action behind the observed association between BMI and parathyroid hormone is unclear, the researchers said. Several studies in patients with normal kidney function indicated that higher BMI was associated with elevated parathyroid hormone levels and lower 1,25(OH)2D and 25(OH)D levels.

Also other measurements have shown that hyperparathyroidism was even better correlated with total body fat, compared with BMI, suggesting that adiposity and not simply higher body weight was responsible for the associations.

Possible explanations for these findings include less sun exposure for obese individuals and higher storage of vitamin D in adipose tissue, or a decreased skeletal response to the actions of parathyroid hormone.

Weight loss by obese patients has been shown to lower their parathyroid hormone levels, the researchers added.

This suggests that weight loss might help lower parathyroid hormone levels in kidney disease patients. Another "intriguing" possibility, the researchers proposed, is an opposite direction for cause and effect, namely that higher hormone levels cause accumulation of fat mass and obesity.

Although it is tempting to extrapolate findings from the general population to kidney-disease patients, important differences between the two groups need to be considered, the researchers emphasized. For example, measurements involving more specific markers of nutritional status and inflammation, such as 25(OH)D, C-reactive protein, IL-6 levels, will be necessary to test these hypotheses.

Study limitations included the exclusive use of male patients from a single institution, the small number of black patients, the lack of measured 1,25(OH)2D and 25(OH)D levels and of specific markers of inflammation, and the retrospective study design, which could not demonstrate causality. Therefore, it was not possible to determine whether obesity induces higher parathyroid hormone levels or vice versa.

Also, the underlying mechanisms of action will have to be better characterized, the researchers concluded.

Dr. Kovesday and co-author Kamyar Kalantar-Zadeh, M.D., Ph.D., reported receiving support from the National Institute of Diabetes, Digestive and Kidney Disease. The study was supported by a grant from Abbott Laboratories to Dr. Kovesday.

Reviewed by Zalman S. Agus, MD Emeritus Professor University of Pennsylvania School of Medicine

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